DESCRIPTION Migraine is a common neurological disorder, affecting nearly 12% of the populations in the US with a high incidence in females. Migraine headache pain can lost hours to days, and causes considerable discomfort, disability and days lost from work Visual symptoms are profound in migraine. Visual aura can occur prior to the onset of migraine pain. Photophobia and vision blurring are associated with most migraine attacks, with or without aura. A neuronal hyperexcitability, particularly in the visual cortex, is a generalized hypothesis in migraine pathophysiology. One mechanism responsible for cortical hyperexcitability might be deficient inhibition by g-aminobutyric acid (GABA)ergic interneurons. In the primary visual cortex, GABAergic neurons form a diffuse horizontal network in lamina IV and are very likely to be selectively vulnerable to hypoperfusion/hypoxia occurring during migraine attack. In response to PA-98-050, the applicants propose to explore an innovative approach to study visual cortical excitability in migraineuers with visual aura by examining excitatory and inhibitory interaction during visual perception. Specifically, they will develop robust psychophysical methods to determine the extent of visual cortical inhibition, both in migraine subjects and non-headache controls, during visual masking. They will develop fMRI methods to determine cortical response to the un-masked (non-inhibited) and masked (inhibited) visual targets in non-headache and migraine individuals. The hypotheses are: (1) The invisible (inhibited) visual target in non-headache controls is visible (non-inhibited) or partially visible (partially non-inhibited) to migraineurs with visual aura in whom visual cortical inhibition is deficient; (2) The non-inhibited visual target in migraineurs induces a neuronal response in primary visual cortex and the inhibited visual target in non-headache controls does not evoke a neuronal response. In order to test the hypotheses, they will develop new fMRI methodologies in image cortical responses to the visual stimuli that are temporally brief (20ms to 100ms), and dimensionally small (subtending 0.5 to 4 degrees of visual angles). There are parameters associated with visual masking. Successful developing these new methodologies is not only crucial for the proposed study, but also extremely valuable for other brain research. Furthermore, the scientific concept proposed here may lead to an innovative approach to investigate visual function/dysfunction in migraine, and may provide a new insight into migraine pathophysiology.